Protective Effects of Water Extract of Fructus Ligustri Lucidi against Oxidative Stress-Related Osteoporosis In Vivo and In Vitro

Wu, Yi; Hu, Yusheng; Zhao, Zhi; Xu, Lei; Chen, Ye; Liu, Tongtong; Li, Qin

doi:10.3390/vetsci8090198

Cited by 9 publications

(9 citation statements)

References 38 publications

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“…ZL201410037992.5). Pharmacological studies show that EF, LLF, and their active ingredients (such as icariin and baohuoside I in EF and oleanolic acid and ursolic acid in LLF) have anti-OP effects through improving bone microstructure, increasing bone mineral density, and promoting the differentiation and proliferation of OBs [9][10][11][12]. The water extract of LLF can upregulate ERα expression of femurs and tibias of ovariectomy-(OVX-) induced OP rats [13]; EF has the estrogen-like effect which is one of the most important mechanisms of EF in treating OP [14].…”

Section: Introductionmentioning

confidence: 99%

Epimedii Folium and Ligustri Lucidi Fructus Promote Osteoblastogenesis and Inhibit Osteoclastogenesis against Osteoporosis via Acting on Osteoblast-Osteoclast Communication

Tang

Chen

et al. 2023

Oxidative Medicine and Cellular Longevity

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Osteoblast (OB) and osteoclast (OC) play important roles in bone formation and bone resorption, which can communicate with each other through cytokine paracrine. Previous studies have confirmed that Epimedii Folium (EF) and Ligustri Lucidi Fructus (LLF) used alone or in combination can treat osteoporosis (OP) through regulating bone remodeling, but the effects of EF and LLF on osteoblastogenesis, osteoclastogenesis, and OB-OC communication are unclear. In this study, we investigated the direct and indirect effects of EF and LLF on OBs and OCs via monoculture and coculture (transwell) models of OBs and OCs. We found that the combination of EF and LLF (EF&LLF) could promote osteoblastogenesis and inhibit osteoclastogenesis directly and indirectly. In order to study the mechanisms of EF&LLF on indirectly regulating osteoblastogenesis and osteoclastogenesis, we detected the expression of cytokines by which OBs and OCs could communicate with each other. We found that EF&LLF could downregulate the expression of RANKL and M-CSF and the protein ratio of RANKL/OPG of OBs and Atp6v0d2 expression of OCs and upregulate the expression of OPG and TGF-β1 of OBs and the expression of TGF-β1, BMP-2, and IGF-1 of OCs, indicating that EF&LLF could regulate cytokine expressions of OBs/OCs to affect OB-OC communication. In addition, EF&LLF had a better effect on regulating cytokines of OBs and OCs than EF or LLF in single use. This study suggested that EF&LLF exhibited the effects of promoting osteoblastogenesis and inhibiting osteoclastogenesis via acting on OB-OC communication and provided some scientific evidences for EF&LLF against OP.

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Section: Introductionmentioning

confidence: 99%

Epimedii Folium and Ligustri Lucidi Fructus Promote Osteoblastogenesis and Inhibit Osteoclastogenesis against Osteoporosis via Acting on Osteoblast-Osteoclast Communication

Tang

Chen

et al. 2023

Oxidative Medicine and Cellular Longevity

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“…To validate the therapeutic effects, in vivo studies were carried out in this work. The bone index and bone dry–wet ratio partially reflected the bone quality of mice . Compared with the control group, the dry–wet ratio of femur and humerus in the model group was significantly decreased (Figure B, P < 0.01).…”

Section: Resultsmentioning

confidence: 90%

“…The experimental validation in this study utilized d -galactose-induced oxidative stress combined with a low-calcium diet to construct an animal model of low-conversion osteoporosis . As shown in micro-CT images, OA significantly alleviated osteoporosis in mice in a dose-dependent manner.…”

Section: Discussionmentioning

confidence: 99%

“…As shown in micro-CT images, OA significantly alleviated osteoporosis in mice in a dose-dependent manner. Moreover, OA could enhance the bone dry to wet ratio by promoting bone salt deposition and accelerating calcification, , thereby improving the bone microarchitecture. Our previous in vitro studies have demonstrated that OA could enhance the cell viability and upregulate the OPG mRNA expression in osteoblasts and regulate the phosphorylation of ERK, JNK, p38, and AKT, which further verified that the osteogenic effects of OA are related to MAPK and AKT signaling pathways .…”

Section: Discussionmentioning

confidence: 99%

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Network Pharmacology-Based Analysis on the Action Mechanism of Oleanolic Acid to Alleviate Osteoporosis

Gao

Fan

et al. 2021

ACS Omega

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Oleanolic acid (OA) is a triterpenoid commonly found in plants and has shown extensive pharmaceutical activities. This study aimed to investigate the underlying mechanism of antiosteoporosis (OP) action of OA by utilizing the network pharmacology approach and molecular docking methods. First, the targets of OA were identified using the GeneCards, Stitch, and Swisstarget databases, and the targets related to OP were mined using the NCBI, Genecards, and DisGeNet databases. The overlapped targets of OA and OP were regarded as candidate targets, and the String database was used to obtain the protein− protein interactions among the targets. Then, Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathway enrichment pathways of the candidate targets were performed using the DAVID database. In addition, the top 16 targets in the protein interaction network were used for molecular docking. Finally, an animal model constructed using D-galactose-induced oxidative stress and a low-calcium diet with accelerated bone loss was used to verify the in vivo effects of OA on osteoporotic mice. A total of 42 candidate targets for OA to treat OP were obtained. According to the protein−protein interaction network, MAPK1 showed the highest connectivity with other proteins. Additionally, GO analysis identified the top 20 biological processes, 9 cellular components, and top 20 molecular functions. Moreover, the candidate targets were mainly involved in 13 signaling pathways such as TNF signaling pathway, insulin resistance, MAPK signaling pathway, apoptosis, and PI3K-Akt signaling pathways. Furthermore, molecular docking revealed that OA has a high degree of connections with 16 key proteins. In addition, the anti-OP effects of OA are further validated through the in vivo model. Altogether, our study elucidated the candidate targets for OA to alleviate OP, explored the protein−protein interactions and related signaling pathways of the targets, and validated the anti-OP effects of OA. It could provide a better understanding of the action mechanism in OA to treat OP.

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“…Pharmacological studies have reported that FLL can promote differentiation of osteoblasts ( 16 ), inhibit osteoclastogenesis ( 17 ), regulate estrogen levels ( 18 ), and regulate BMD and bone properties via certain pathways, such as the Wnt/β-catenin ( 19 ), NADPH oxidase 4/ROS/NF-κB ( 20 ) and TGF-β1/Smads signaling pathways ( 21 ). Furthermore, FLL also inhibits oxidative stress ( 22 , 23 ) and FLL has been reported to be associated with iron overload ( 24 ). The nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway is an important pathway against oxidative stress and regulates iron and lipid metabolism ( 25 ).…”

Section: Introductionmentioning

confidence: 99%

Fructus Ligustri Lucidi inhibits ferroptosis in ovariectomy‑induced osteoporosis in rats via the Nrf2/HO‑1 signaling pathway

Li,

Wang,

Yan

et al. 2023

Biomed Rep

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Postmenopausal osteoporosis (PMOP) has increased in prevalence in recent years, thus researchers have evaluated alternative medicine therapies. Fructus Ligustri Lucidi (FLL) can inhibit bone loss, and ferroptosis serves an important role in osteoporosis. Therefore, the present study assessed the presence of ferroptosis in PMOP and whether FLL could inhibit ferroptosis to improve bone microstructure in ovariectomized rats. Ovariectomized rats were treated with FLL (1.56 g/kg/day) for 12 weeks. Micro-CT was performed to evaluate the bone microstructure and bone mineral density. Western blotting and reverse transcription-quantitative PCR were performed to assess the relative expression levels of proteins and mRNA. Subsequently, malondialdehyde (MDA) and Fe 2+ assay kits were used to quantify the MDA and Fe 2+ content, respectively. The results demonstrated that ovariectomy (OVX) resulted in iron overload and the accumulation of lipid peroxide. Furthermore, the expression of key factors that inhibited ferroptosis, glutathione peroxidase 4 and solute carrier family 7 member 11 was significantly downregulated in ovariectomized rats, which was significantly reversed by FLL treatment. Furthermore, bone formation was assessed using the expression of osteogenesis-related genes, runt-related transcription factor 2 and osterix, which revealed significantly higher levels in FLL-treated rats compared with ovariectomized rats. The levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) were also significantly recovered following FLL treatment. In the present study, OVX of postmenopausal osteoporotic rats was found to induce ferroptosis by enhancing lipid peroxidation and Fe 2+ levels. FLL significantly suppressed ferroptosis, protected the osteogenic ability of ovariectomized rats and promoted the Nrf2/HO-1 signaling pathway.

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Protective Effects of Water Extract of Fructus Ligustri Lucidi against Oxidative Stress-Related Osteoporosis In Vivo and In Vitro

Cited by 9 publications

References 38 publications

Epimedii Folium and Ligustri Lucidi Fructus Promote Osteoblastogenesis and Inhibit Osteoclastogenesis against Osteoporosis via Acting on Osteoblast-Osteoclast Communication

Epimedii Folium and Ligustri Lucidi Fructus Promote Osteoblastogenesis and Inhibit Osteoclastogenesis against Osteoporosis via Acting on Osteoblast-Osteoclast Communication

Network Pharmacology-Based Analysis on the Action Mechanism of Oleanolic Acid to Alleviate Osteoporosis

Fructus Ligustri Lucidi inhibits ferroptosis in ovariectomy‑induced osteoporosis in rats via the Nrf2/HO‑1 signaling pathway

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